Alzheimer's disease: cerebrovascular dysfunction, oxidative stress, and advanced clinical therapies.
Many lines of independent research have provided convergent evidence regarding oxidative stress, cerebrovascular disease, dementia, and Alzheimer's disease (AD). Clinical studies spurred by these findings engage basic and clinical communities with tangible results regarding molecular targets and patient outcomes. Focusing on recent progress in characterizing age-related diseases specifically highlights oxidative stress and mechanisms for therapeutic action in AD. Oxidative stress has been investigated independently for its relationship with aging and cardiovascular and neurodegenerative diseases and provides evidence of shared pathophysiology across these conditions. The mechanisms by which oxidative stress impacts the cerebrovasculature and blood-brain barrier are of critical importance for evaluating antioxidant therapies. Clinical research has identified homocysteine as a relevant risk factor for AD and dementia; basic research into molecular mechanisms associated with homocysteine metabolism has revealed important findings. Oxidative stress has direct implications in the pathogenesis of age-related neurodegenerative diseases and careful scrutiny of oxidative stress in the CNS has therapeutic implications for future clinical trials. These mechanisms of dysfunction, acting independently or in concert, through oxidative stress may provide the research community with concise working concepts and promising new directions to yield new methods for evaluation and treatment of dementia and AD.
Marlatt
Michael W
MW
Swammerdam Institute for Life Sciences - Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands.
Lucassen
Paul J
PJ
Perry
George
G
Smith
Mark A
MA
Zhu
Xiongwei
X
D000544:Alzheimer Disease / Q000150:complications* / Q000628:therapy*; D002561:Cerebrovascular Disorders / Q000150:complications / Q000209:etiology* / Q000523:psychology / Q000628:therapy*; D002986:Clinical Trials as Topic; D003704:Dementia / Q000209:etiology / Q000523:psychology; D006710:Homocysteine / Q000502:physiology; D006801:Humans; D019636:Neurodegenerative Diseases / Q000628:therapy; D018384:Oxidative Stress / Q000502:physiology*
D006710:Homocysteine